tbuckley/cabot-search huggingface dataset:
Rb Tumor Suppressor in Small Cell Lung Cancer: Combined Genomic and IHC Analysis with a Description of a Distinct Rb-Proficient Subset
Authors: Christopher A. Febres-Aldana, Jason C. Chang, Ryan Ptashkin, Yuhan Wang, Erika Gedvilaite, Marina K. Baine, William D. Travis, Katia Ventura, Francis Bodd, Helena A. Yu, Alvaro Quintanal-Villalonga, W. Victoria Lai, Jacklynn V. Egger, Michael Offin, Marc Ladanyi, Charles M. Rudin, Natasha Rekhtman
Journal: Clinical Cancer Research (2022)

Abstract Purpose: RB1 mutations and loss of retinoblastoma (Rb) expression represent consistent but not entirely invariable hallmarks of small cell lung cancer (SCLC). The prevalence and characteristics of SCLC retaining wild-type Rb are not well-established. Furthermore, the performance of targeted next-generation sequencing (NGS) versus immunohistochemistry for Rb assessment is not well-defined. Experimental Design: A total of 208 clinical SCLC samples were analyzed by comprehensive targeted NGS, covering all exons of RB1, and Rb IHC. On the basis of established coordination of Rb/p16/cyclinD1 expression, p16-high/cyclinD1-low profile was used as a marker of constitutive Rb deficiency. Results: Fourteen of 208 (6%) SCLC expressed wild-type Rb, accompanied by a unique p16-low/cyclinD1-high profile supporting Rb proficiency. Rb-proficient SCLC was associated with neuroendocrine-low phenotype, combined SCLC with non-SCLC (NSCLC) histology and aggressive behavior. These tumors exclusively harbored CCND1 amplification (29%), and were markedly enriched in CDKN2A mutations (50%) and NSCLC-type alterations (KEAP1, STK11, FGFR1). The remaining 194 of 208 SCLC were Rb-deficient (p16-high/cyclinD1-low), including 184 cases with Rb loss (of which 29% lacked detectable RB1 alterations by clinical NGS pipeline), and 10 cases with mutated but expressed Rb. Conclusions: This is the largest study to date to concurrently analyze Rb by NGS and IHC in SCLC, identifying a 6% rate of Rb proficiency. Pathologic-genomic data implicate NSCLC-related progenitors as a putative source of Rb-proficient SCLC. Consistent upstream Rb inactivation via CDKN2A/p16↓ and CCND1/cyclinD1↑ suggests the potential utility of CDK4/6 inhibitors in this aggressive SCLC subset. The study also clarifies technical aspects of Rb status determination in clinical practice, highlighting the limitations of exon-only sequencing for RB1 interrogation. See related commentary by Mahadevan and Sholl, p. 4603
Combined molecular subtyping, grading, and segmentation of glioma using multi-task deep learning
Authors: Sebastian R van der Voort, Fatih Incekara, Maarten M J Wijnenga, Georgios Kapsas, Renske Gahrmann, Joost W Schouten, Rishi Nandoe Tewarie, Geert J Lycklama, Philip C De Witt Hamer, Roelant S Eijgelaar, Pim J French, Hendrikus J Dubbink, Arnaud J P E Vincent, Wiro J Niessen, Martin J van den Bent, Marion Smits, Stefan Klein
Journal: Neuro-Oncology (2022)

Abstract Background Accurate characterization of glioma is crucial for clinical decision making. A delineation of the tumor is also desirable in the initial decision stages but is time-consuming. Previously, deep learning methods have been developed that can either non-invasively predict the genetic or histological features of glioma, or that can automatically delineate the tumor, but not both tasks at the same time. Here, we present our method that can predict the molecular subtype and grade, while simultaneously providing a delineation of the tumor. Methods We developed a single multi-task convolutional neural network that uses the full 3D, structural, preoperative MRI scans to predict the IDH mutation status, the 1p/19q co-deletion status, and the grade of a tumor, while simultaneously segmenting the tumor. We trained our method using a patient cohort containing 1508 glioma patients from 16 institutes. We tested our method on an independent dataset of 240 patients from 13 different institutes. Results In the independent test set, we achieved an IDH-AUC of 0.90, an 1p/19q co-deletion AUC of 0.85, and a grade AUC of 0.81 (grade II/III/IV). For the tumor delineation, we achieved a mean whole tumor Dice score of 0.84. Conclusions We developed a method that non-invasively predicts multiple, clinically relevant features of glioma. Evaluation in an independent dataset shows that the method achieves a high performance and that it generalizes well to the broader clinical population. This first-of-its-kind method opens the door to more generalizable, instead of hyper-specialized, AI methods.
Leading Causes of Death in the US During the COVID-19 Pandemic, March 2020 to October 2021
Authors: Meredith S. Shiels, Anika T. Haque, Amy Berrington de González, Neal D. Freedman
Journal: JAMA Internal Medicine (2022)

Using national death certificate data for 2020 and provisional data for 2021 from the Centers for Disease Control and Prevention, this cross-sectional study examines the leading causes of death in the US, overall and in various age groups.
Human complete NFAT1 deficiency causes a triad of joint contractures, osteochondromas, and B-cell malignancy
Authors: Mehul Sharma, Maggie P. Fu, Henry Y. Lu, Ashish A. Sharma, Bhavi P. Modi, Christina Michalski, Susan Lin, Joshua Dalmann, Areesha Salman, Kate L. Del Bel, Meriam Waqas, Jefferson Terry, Audi Setiadi, Pascal M. Lavoie, Wyeth W. Wasserman, Jill Mwenifumbo, Michael S. Kobor, Anna F. Lee, Florian Kuchenbauer, Anna Lehman, Sylvia Cheng, Anthony Cooper, Millan S. Patel, Stuart E. Turvey
Journal: Blood (2022)
Baseline clinical characteristics of heart failure patients with reduced ejection fraction enrolled in the BUDAPEST‐CRT Upgrade trial
Authors: Béla Merkely, László Gellér, Endre Zima, István Osztheimer, Levente Molnár, Csaba Földesi, Gábor Duray, Jerzy K. Wranicz, Marianna Németh, Kinga Goscinska‐Bis, Robert Hatala, László Sághy, Boglárka Veres, Walter Richard Schwertner, Alexandra Fábián, Eszter Fodor, Ilan Goldenberg, Valentina Kutyifa, Attila Kovács, Annamária Kosztin
Journal: European Journal of Heart Failure (2022)
Prevalence of Autism Spectrum Disorder Among Children and Adolescents in the United States From 2019 to 2020
Authors: Qian Li, Yanmei Li, Buyun Liu, Qingsong Chen, Xiaohui Xing, Guifeng Xu, Wenhan Yang
Journal: JAMA Pediatrics (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2022 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Chronic phase CML with sole P190 (e1a2) BCR::ABL1: long-term outcome among ten consecutive cases
Authors: Maymona G. Abdelmagid, Mark R. Litzow, Kristen B. McCullough, Naseema Gangat, Animesh Pardanani, Hemant S. Murthy, James M. Foran, Rhett P. Ketterling, David Viswanatha, Kebede H. Begna, Ayalew Tefferi
Journal: Blood Cancer Journal (2022)
Can Peanut Allergy Prevention Be Translated to the Pediatric Population?
Authors: Jennifer Dantzer, Robert A. Wood
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Diversity in EWAS: current state, challenges, and solutions
Authors: Charles E. Breeze, Jason Y. Y. Wong, Stephan Beck, Sonja I. Berndt, Nora Franceschini
Journal: Genome Medicine (2022)

Here, we report a lack of diversity in epigenome-wide association studies (EWAS) and DNA methylation (DNAm) data, discuss current challenges, and propose solutions for EWAS and DNAm research in diverse populations. The strategies we propose include fostering community involvement, new data generation, and cost-effective approaches such as locus-specific analysis and ancestry variable region analysis.
Targeted delivery of lipid nanoparticle to lymphatic endothelial cells via anti-podoplanin antibody
Authors: Yu Sakurai, Nodoka Abe, Keito Yoshikawa, Ryotaro Oyama, Satoshi Ogasawara, Takeshi Murata, Yuta Nakai, Kota Tange, Hiroki Tanaka, Hidetaka Akita
Journal: Journal of Controlled Release (2022)
Dual αV-integrin and neuropilin-1 targeting peptide CEND-1 plus nab-paclitaxel and gemcitabine for the treatment of metastatic pancreatic ductal adenocarcinoma: a first-in-human, open-label, multicentre, phase 1 study
Authors: Andrew Dean, Sanjeev Gill, Mark McGregor, Vy Broadbridge, Harri A Järveläinen, Timothy Price
Journal: The Lancet. Gastroenterology & hepatology (2022)
Guideline‐directed medical therapy in patients undergoing transcatheter edge‐to‐edge repair for secondary mitral regurgitation
Authors: Satoshi Higuchi, Mathias Orban, Marianna Adamo, Cristina Giannini, Bruno Melica, Nicole Karam, Fabien Praz, Daniel Kalbacher, Benedikt Koell, Lukas Stolz, Daniel Braun, Michael Näbauer, Mirjam Wild, Philipp Doldi, Michael Neuss, Christian Butter, Mohammad Kassar, Tobias Ruf, Aniela Petrescu, Sebastian Ludwig, Roman Pfister, Christos Iliadis, Matthias Unterhuber, Francisco Sampaio, Diogo Ferreira, Holger Thiele, Stephan Baldus, Ralph Stephan von Bardeleben, Steffen Massberg, Stephan Windecker, Philipp Lurz, Anna Sonia Petronio, JoAnn Lindenfeld, William T. Abraham, Marco Metra, Jörg Hausleiter
Journal: European Journal of Heart Failure (2022)

Guideline-directed medical therapy (GDMT), based on the combination of beta-blockers (BB), renin-angiotensin system inhibitors (RASI), and mineralocorticoid receptor antagonists (MRA), is known to have a major impact on the outcome of patients with heart failure with reduced ejection fraction (HFrEF). Although GDMT is recommended prior to mitral valve transcatheter edge-to-edge repair (M-TEER), not all patients tolerate it. We studied the association of GDMT prescription with survival in HFrEF patients undergoing M-TEER for secondary mitral regurgitation (SMR).EuroSMR, a European multicentre registry, included SMR patients with left ventricular ejection fraction <50%. The outcome was 2-year all-cause mortality. Of 1344 patients, BB, RASI, and MRA were prescribed in 1169 (87%), 1012 (75%), and 765 (57%) patients at the time of M-TEER, respectively. Triple GDMT prescription was associated with a lower 2-year all-cause mortality compared to non-triple GDMT (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.60-0.91). The association persisted in patients with glomerular filtration rate <30 ml/min, ischaemic aetiology, or right ventricular dysfunction. Further, a positive impact of triple GDMT prescription on survival was observed in patients with residual mitral regurgitation of ≥2+ (HR 0.62; 95% CI 0.44-0.86), but not in patients with residual mitral regurgitation of ≤1+ (HR 0.83; 95% CI 0.64-1.08).Triple GDMT prescription is associated with higher 2-year survival after M-TEER in HFrEF patients with SMR. This association was consistent also in patients with major comorbidities or non-optimal results after M-TEER.
Association Between Earlier Introduction of Peanut and Prevalence of Peanut Allergy in Infants in Australia
Authors: Victoria X. Soriano, Rachel L. Peters, Margarita Moreno-Betancur, Anne-Louise Ponsonby, Grace Gell, Alexsandria Odoi, Kirsten P. Perrett, Mimi L. K. Tang, Lyle C. Gurrin, Katrina J. Allen, Shyamali C. Dharmage, Jennifer J. Koplin
Journal: JAMA (2022)

Randomized clinical trials showed that earlier peanut introduction can prevent peanut allergy in select high-risk populations. This led to changes in infant feeding guidelines in 2016 to recommend early peanut introduction for all infants to reduce the risk of peanut allergy.
Racial bias and reproducibility in pulse oximetry among medical and surgical inpatients in general care in the Veterans Health Administration 2013-19: multicenter, retrospective cohort study
Authors: Valeria S M Valbuena, Sarah Seelye, Michael W Sjoding, Thomas S Valley, Robert P Dickson, Steven E Gay, Dru Claar, Hallie C Prescott, Theodore J Iwashyna
Journal: BMJ (2022)

Abstract Objectives To evaluate measurement discrepancies by race between pulse oximetry and arterial oxygen saturation (as measured in arterial blood gas) among inpatients not in intensive care. Design Multicenter, retrospective cohort study using electronic medical records from general care medical and surgical inpatients. Setting Veteran Health Administration, a national and racially diverse integrated health system in the United States, from 2013 to 2019. Participants Adult inpatients in general care (medical and surgical), in Veteran Health Administration medical centers. Main outcomes measures Occult hypoxemia (defined as arterial blood oxygen saturation (SaO 2 ) of &lt;88% despite a pulse oximetry (SpO 2 ) reading of ≥92%), and whether rates of occult hypoxemia varied by race and ethnic origin. Results A total of 30 039 pairs of SpO 2 -SaO 2 readings made within 10 minutes of each other were identified during the study. These pairs were predominantly among non-Hispanic white (21 918 (73.0%)) patients; non-Hispanic black patients and Hispanic or Latino patients accounted for 6498 (21.6%) and 1623 (5.4%) pairs in the sample, respectively. Among SpO 2 values greater or equal to 92%, unadjusted probabilities of occult hypoxemia were 15.6% (95% confidence interval 15.0% to 16.1%) in white patients, 19.6% (18.6% to 20.6%) in black patients (P&lt;0.001 v white patients, with similar P values in adjusted models), and 16.2% (14.4% to 18.1%) in Hispanic or Latino patients (P=0.53 v white patients, P&lt;0.05 in adjusted models). This result was consistent in SpO 2 -SaO 2 pairs restricted to occur within 5 minutes and 2 minutes. In white patients, an initial SpO 2 -SaO 2 pair with little difference in saturation was associated with a 2.7% (95% confidence interval −0.1% to 5.5%) probability of SaO 2 &lt;88% on a later paired SpO 2 -SaO 2 reading showing an SpO 2 of 92%, but black patients had a higher probability (12.9% (−3.3% to 29.0%)). Conclusions In general care inpatient settings across the Veterans Health Administration where paired readings of arterial blood gas (SaO 2 ) and pulse oximetry (SpO 2 ) were obtained, black patients had higher odds than white patients of having occult hypoxemia noted on arterial blood gas but not detected by pulse oximetry. This difference could limit access to supplemental oxygen and other more intensive support and treatments for black patients.
Evaluation of a multicomponent intervention to shorten thrombolytic door-to-needle time in stroke patients in China (MISSION): A cluster-randomized controlled trial
Authors: Wansi Zhong, Longting Lin, Xiaoxian Gong, Zhicai Chen, Yi Chen, Shenqiang Yan, Ying Zhou, Xuting Zhang, Haitao Hu, Lusha Tong, Chaochan Cheng, Qun Gu, Yong Chen, Xiaojin Yu, Yuhui Huang, Changzheng Yuan, Min Lou
Journal: PLoS Medicine (2022)

Background Rapid intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) is crucial for improving outcomes. However, few randomized trials of interventions aimed at reducing in-hospital delay have been carried out in China. We aimed to evaluate the effect of a multicomponent intervention on thrombolytic door-to-needle time (DNT) of AIS patients via video teleconference based on the Behavior Change Wheel (BCW) method. Methods and findings This cluster-randomized trial, conducted between January 1, 2019 and December 31, 2019, randomly allocated 22 hospitals equally to PEITEM (Persuasion Environment reconstruction Incentivization Training Education Modeling) intervention or routine care plus stroke registry and subsequently enrolled 1,634 AIS patients receiving IVT within 4.5 hours upon stroke onset from participant hospitals. The PEITEM group received a 1-year PEITEM 6-component intervention based on the behavioral theory monthly via video teleconference. The primary outcome was the proportion of patients with a DNT of 60 minutes or less. A total of 987 patients participated in the PEITEM group (mean age, 69 years; female, 411 [41.6%]) and 647 patients in the control group (mean age, 70 years; female, 238 [36.8%]). Of all participants, the proportion of DNT ≤60 minutes in the PEITEM group was higher than in the control group (82.0% versus 73.3%; adjusted odds ratio, 1.77; 95% confidence interval (CI), 1.17 to 2.70; ICC, 0.04; P = 0.007). Among secondary outcomes, the average DNT was 43 minutes in the PEITEM group and 50 minutes in the control group (adjusted mean difference: −8.83; 95% CI, −14.03 to −3.64; ICC, 0.12; P = 0.001). Favorable functional outcome (score of 0 to 1 on the modified Rankin scale (mRS)) was achieved in 55.6% patients of the PEITEM group and 50.4% of the control group (adjusted odds ratio, 1.38; 95% CI, 1.00 to 1.90; ICC, 0.01; P = 0.049). Main study limitations include non-blinding of clinicians, and that specific interventions component responsible for the observed changes could not be determined. Conclusions The teleconference-delivered PEITEM intervention resulted in a moderate but clinically relevant shorter DNT and better functional outcome in AIS patients receiving IVT. Trial registration Clinicaltrials.gov NCT03317639 .
Threshold-free genomic cluster detection to track transmission pathways in health-care settings: a genomic epidemiology analysis
Authors: Shawn E Hawken, Rachel D Yelin, Karen Lolans, Ali Pirani, Robert A Weinstein, Michael Y Lin, Mary K Hayden, Evan S Snitkin
Journal: The Lancet Microbe (2022)

A crucial barrier to the routine application of whole-genome sequencing (WGS) for infection prevention is the insufficient criteria for determining whether a genomic linkage is consistent with transmission within the facility. We evaluated the use of single-nucleotide variant (SNV) thresholds, as well as a novel threshold-free approach, for inferring transmission linkages in a high-transmission setting.We did a retrospective genomic epidemiology analysis of samples previously collected in the context of an intervention study at a long-term acute care hospital in the USA. We performed WGS on 435 isolates of Klebsiella pneumoniae harbouring the blaKPC carbapenemase (KPC-Kp) collected from 256 patients through admission and surveillance culturing (once every 2 weeks) of almost every patient who was admitted to hospital over a 1-year period.Our analysis showed that the standard approach of using an SNV threshold to define transmission would lead to false-positive and false-negative inferences. False-positive inferences were driven by the frequent importation of closely related strains, which were presumably linked via transmission at connected health-care facilities. False-negative inferences stemmed from the diversity of colonising populations that were spread among patients, with multiple examples of hypermutator strain emergence within patients and, as a result, putative transmission links separated by large genetic distances. Motivated by limitations of an SNV threshold, we implemented a novel threshold-free transmission cluster inference approach, in which each of the acquired KPC-Kp isolates were linked back to the imported KPC-Kp isolate with which it shared the most variants. This approach yielded clusters that varied in levels of genetic diversity but where 105 (81%) of 129 unique strain acquisition events were associated with epidemiological links in the hospital. Of 100 patients who acquired KPC-Kp isolates that were included in a cluster, 47 could be linked to a single patient who was positive for KPC-Kp at admission, compared with 31 and 25 using 10 SNV and 20 SNV thresholds, respectively. Holistic examination of clusters highlighted extensive variation in the magnitude of onward transmission stemming from more than 100 importation events and revealed patterns in cluster propagation that could inform improvements to infection prevention strategies.Our results show how the integration of culture surveillance data into genomic analyses can overcome limitations of cluster detection based on SNV-thresholds and improve the ability to track pathways of pathogen transmission in health-care settings.US Center for Disease Control and Prevention and University of Michigan.
Breakthrough <scp>SARS</scp> – <scp>CoV</scp> ‐2 Infections in Patients With <scp>Immune‐Mediated</scp> Disease Undergoing B Cell–Depleting Therapy: A Retrospective Cohort Analysis
Authors: Cassandra M. Calabrese, Elizabeth Kirchner, Elaine M. Husni, Brandon P. Moss, Anthony P. Fernandez, Yuxuan Jin, Leonard H. Calabrese
Journal: Arthritis & Rheumatology (2022)

Patients with immune-mediated inflammatory diseases (IMIDs) receiving B cell-depleting therapy (BCDT) are among the most vulnerable to severe COVID-19, as well as the most likely to suboptimally respond to SARS-CoV-2 vaccines. However, little is known about the frequency or severity of breakthrough infection in this population. We retrospectively analyzed a large group of vaccinated IMID patients undergoing BCDT in order to identify breakthrough COVID-19 infections and assess their outcomes.In this retrospective cohort study, the pharmacy records and COVID-19 registry at the Cleveland Clinic were searched using specific International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes to identify IMIDs patients who 1) received treatment with BCDT, 2) were vaccinated against SARS-CoV-2, and 3) experienced breakthrough infections. Each electronic medical record was reviewed to extract clinical data and outcomes. Univariate and multivariable logistic/proportional odds regression models were used to examine the risk factors for severe outcomes.Of 1,696 IMID patients receiving BCDT, 74 developed breakthrough COVID-19 prior to December 16, 2021. Outcomes were severe, with 29 patients hospitalized (39.2%), 11 patients requiring critical care (14.9%), and 6 deaths (8.1%). Outpatient anti-SARS-CoV-2 monoclonal antibodies were used to treat 21 patients, with 1 hospitalization and no deaths. A comparator analysis examining 1,437 unvaccinated IMID patients receiving BCDT over the same time period identified 57 COVID-19 cases (4.0%), with 28 requiring hospitalization (49.1%), including 7 deaths (12.3%).IMID patients receiving BCDT regardless of vaccine status appear to be vulnerable to infection with SARS-CoV-2, and use of BCDT is frequently associated with severe outcomes. Outpatient use of anti-SARS-CoV-2 monoclonal antibody therapy appears to be associated with enhanced clinical outcomes.